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Neurobehavioral and Imaging Correlates of Hippocampal Atrophy in a Mouse Model of Vascular Cognitive Impairment

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Abstract

Vascular cognitive impairment (VCI) is the second most common cause of dementia. Reduced cerebral blood flow is thought to play a major role in the etiology of VCI. Therefore, chronic cerebral hypoperfusion has been used to model VCI in rodents. The goal of the current study was to determine the histopathological and neuroimaging substrates of neurocognitive impairments in a mouse model of chronic cerebral hypoperfusion induced by unilateral common carotid artery occlusion (UCCAO). Mice were subjected to sham or right UCCAO (VCI) surgeries. Three months later, neurocognitive function was evaluated using the novel object recognition task, Morris water maze, and contextual and cued fear-conditioning tests. Next, cerebral perfusion was evaluated with dynamic susceptibility contrast magnetic resonance imaging (MRI) using an ultra-high field (11.75 T) animal MRI system. Finally, brain pathology was evaluated using histology and T2-weighted MRI. VCI, but not sham, mice had significantly reduced cerebral blood flow in the right vs. left cerebral cortex. VCI mice showed deficits in object recognition. T2-weighted MRI of VCI brains revealed enlargement of lateral ventricles, which corresponded to areas of hippocampal atrophy upon histological analysis. In conclusion, our data demonstrate that the UCCAO model of chronic hypoperfusion induces hippocampal atrophy and ventricular enlargement, resulting in neurocognitive deficits characteristic of VCI.

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Acknowledgments

The authors would like to acknowledge Erin Bidiman and Massarra Eiwaz for their assistance with the behavioral testing.

Compliance with Ethical Standards

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Funding

This study was funded by the National Institutes of Health grants R21AG043857 (NJA), R01NS070837 (NJA), and F32NS082017 (KLZ) and the development account of JR.

Conflict of Interest

The authors declare that they have no competing interests.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Authors and Affiliations

  1. Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, UHN-2, Portland, OR, 97239, USA

    Kristen L. Zuloaga, Wenri Zhang, Xiao Nie, Natalie E. Roese, Marjorie R. Grafe & Nabil J. Alkayed

  2. The Knight Cardiovascular Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, UHN-2, Portland, OR, 97239, USA

    Jacob Raber & Nabil J. Alkayed

  3. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, 97239, USA

    Lauren A. Yeiser, Blair Stewart & Jacob Raber

  4. Advanced Imaging Resource Center, Oregon Health & Science University, Portland, OR, 97239, USA

    Ayaka Kukino & Martin M. Pike

  5. Department of Pathology, Oregon Health & Science University, Portland, OR, 97239, USA

    Marjorie R. Grafe

  6. Radiation Medicine and Neurology, Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR, 97239, USA

    Jacob Raber

Authors
  1. Kristen L. Zuloaga
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  2. Wenri Zhang
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  3. Lauren A. Yeiser
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  4. Blair Stewart
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  5. Ayaka Kukino
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  6. Xiao Nie
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  7. Natalie E. Roese
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  8. Marjorie R. Grafe
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  9. Martin M. Pike
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  10. Jacob Raber
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  11. Nabil J. Alkayed
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Corresponding author

Correspondence to Nabil J. Alkayed.

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Zuloaga, K.L., Zhang, W., Yeiser, L.A. et al. Neurobehavioral and Imaging Correlates of Hippocampal Atrophy in a Mouse Model of Vascular Cognitive Impairment. Transl. Stroke Res. 6, 390–398 (2015). https://doi.org/10.1007/s12975-015-0412-z

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  • DOI: https://doi.org/10.1007/s12975-015-0412-z

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